Dose reductions in ibrutinib therapy are not associated with inferior outcomes in patients with chronic lymphocytic leukemia (CLL)

Leuk Lymphoma. 2019 Jul;60(7):1650-1655. doi: 10.1080/10428194.2018.1554862. Epub 2019 Jan 2.

Abstract

Ibrutinib is a first-in-class small molecule inhibitor that has shown remarkable efficacy in the treatment of CLL. Current guidelines recommend lifelong administration at a fixed daily dose of 420 mg. Data from real-world studies indicate up to 17.5% of patients discontinue ibrutinib due to toxicity. Hypothetically, judicious dose reductions could result in improved tolerance. Our objective was to study the impact of dose reductions on outcomes in CLL patients treated with ibrutinib in a real-world setting. We identified 70 CLL patients treated with ibrutinib at Roswell Park Comprehensive Cancer Center between January 2014 and June 2017. Twenty-three (31.3%) patients required dose reductions. There was no statistically significant difference in overall response rate (ORR), clinical benefit rate (CBR), median progression-free survival, and overall survival (OS) between the dose-reduced and standard-dose groups (SDGs). These results extended to all patients, irrespective of whether the modification was made within three months of treatment initiation, or later.

Keywords: Lymphoid leukemia; pharmacotherapeutics; signal transduction; signaling therapies.

MeSH terms

  • Adenine / analogs & derivatives
  • Aged
  • Aged, 80 and over
  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy
  • Leukemia, Lymphocytic, Chronic, B-Cell / mortality*
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Male
  • Middle Aged
  • Piperidines
  • Prognosis
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrazoles / therapeutic use*
  • Pyrimidines / therapeutic use*
  • Retrospective Studies
  • Survival Rate

Substances

  • Piperidines
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyrimidines
  • ibrutinib
  • Adenine